Detomidine which is 4-[(2,3-dimethylbenzyl)]imidazole of formula I

is a well known pharmaceutical agent currently used as its hydrochloride salt in veterinary use. Detomidine injectable solution (Domosedan®, Dormosedan®) is used for sedation and analgesia of horses and cattle during various examinations and treatments. Detomidine and its preparation are described in U.S. Pat. Nos. 4,443,466 and 4,584,383.
Administration of detomidine hydrochloride by injection provides rapid and reliable sedation in large animals, but the dosage form has to be given by a skilled animal care provider such as a veterinarian. Moreover, some large animals are “needle shy” which can make the administration by injection difficult. Therefore, other means for administering detomidine have been attempted.
Transmucosal administration by “squirting” detomidine injectable solution sublingually has been described (Malone, J. H. and Clarke K. W., J. Vet. Anaest., 20, Dec. 1993, 73-77). Useful sedation was achieved at the dose of 40 μg/kg by this method, but the rate at which the sedation developed (45 minutes for maximal effects) was substantially slower than after intramuscular injection.
In another study, detomidine injectable solution was delivered from a plastic syringe into the buccal or oral cavity of the horse as such or mixed with different food mediums such as apple sauce and gum mixture or molasses (Ramsay, E. C. et al, Veterinary Anaesthesia an Analgesia, 2002, 29, 219-222). The dose of 60 μg/kg was needed to produce adequate level of sedation, which produced profound head droop in horses in approximately 45 minutes.
Finally, transmucosal adhesive patches for veterinary use have been described in the International Patent Publication WO 00/19987 detomidine being mentioned as one of the suitable active agents. However, the present applicant has found that such transmucosal patch dosage forms of detomidine cause substantial, unacceptable local irritation if applied to oral mucosa of large animals such as horse. This irritation is most likely caused by the active agent detomidine itself and therefore it was found to be a major obstacle for the therapeutic administration of detomidine via transmucosal patch formulations.
Hence, there is still a need for improved products for the administration of detomidine in large animals such as horses and cattle, such products providing rapid onset of action, easy administration and low irritation potential.